Layered lyophilized product in a disposable syringe



22, 1967 c. w. DAMASKUS 3,337,041

BLE SYRINGE LAYERED LYOFHILIZED PRODUCT IN A UISPOSA I 2 Sheets-$heetFiled Oct. 23, 1965 1967 c. w. DAMASKUS 3,337,041

LAYERED LYOPHILIZE'D PRODUCT IN A Filed Oct. 23, 1965 DISPOSABLE SYRINGE2 Sheets-Sheet United States Patent Office 3,337, 64. 1 Patented Aug.22, 1967 3,337,041 LAYERED LYUPHILIZED PRGDUCT IN A IDKSPUSABLE SYRHNGECharles W. Damaskus, 703 Madison, La Grange, ill. 60525 Filed Oct. 23,1965, Ser. No. 5i 3,224 9 iClaims. (Cl. 20663.2)

This invention relates to pharmaceuticals, and to methods and apparatusfor dispensing pharmaceuticals, and concerns particularly a novelpharmaceutical package particuarly adapted to facilitate the making of apharmaceutical solution, and the administering thereof to a patient.

In the administering of pharmaceutical solutions, as for exampleintravenous post-operative injections, two methods are now commonlyemployed. In accordance with one commonly used method, a specialcontainer is used, containing in dry form the pharmaceutical or themedicine to be administered. Such special container is provided with aspecial penetrating point adapted for cooperation with a special stopperof a second container filled with a liquid solvent or the like, so thatby an exchange of the liquid between the containers the drypharmaceutical may be reconstituted and subsequently administered, asfor example by use of a standard syringe. The disadvantage of theforegoing is that special apparatus, and special techniques andprocedures are required, frequently requiring special instruction ofoperating personnel.

A second method now employed involves the use of andard containers and astandard syringe throughout, which, while employing standard apparatusand techniques, is generally cumbersome and slow in operation.

In accordance with the present invention, maceutic-al package isprepared, erally standard syringe, within which is pharmaceutical,preferably in layered lyophilized form. The unit is so arranged that thepharmaceutical may be readily reconstituted within the syringe, bymanipulation of the syringe in accordance with standard techniques, andthe reconstituted pharmaceutical thereafter administered to a patient,again by manipulation of the syringe in accordance with standardtechniques, tire operation may be carried out by personnel usingstandard techniques with which they are familiar, but also in a rapidand facile manner. Preferably the package is so constructed that itssterility is preserved and insured, and the reconstitution of thepharmaceutical is facilitated 'so that in most instances it may besubstantially instantaneous.

Preferably, but not necessarily, the dry pharmaceutical within thesyringe, and comprising the novel package of the present invention, maybe in layered lyophilized form, and prepared in accordance with thegeneral method set forth in the application to Charles W. Damaskus andJames E. Alder, Ser. No. 487,109, filed Sept. 14, 1965, and now issuedas Patent No. 3,269,905, dated Aug. 30, 1966.

An object of the present invention is to provide a novel pharmaceuticalpackage, comprising in part, a syringe of generally standard structure,and a pharmaceutical contained therein, in dried readily reconstitutableform.

A further object of the invention is to provide a novel pharmaceuticalpackage of the type defined, wherein the contained pharmaceutical is inlayered lyophilized form.

A still further object of the invention is to provide in apharmaceutical package of the type defined, improved means forinsuringand maintaining the sterility of the package, and means for facilitatingthe reconstitution of the pharmaceutical material.

Another object of the present invention is to provide a whereby the enacontained dry pharmaceutical, and administer the reintravenously to apatient.

Various other objects, advantages and features of the invention will beapparent from the following specification when taken in connection withthe accompanying drawings, wherein a preferred embodiment of theinvention is set forth for purposes of illustration.

In the drawings, wherein like reference numerals refer to like partsthroughout:

FIG. 1 is an exploded view of a syringe structure forming a part of thenovel pharmaceutical package hereof;

FIG. 2 is a longitudinal sectional view of the syringe structure of FIG.1, on an enlarged scale, showing the pharmaceutical package in completedform, prior to use;

FIG. 3 is a longitudinal sectional View, similar to FIG. 2, but showingthe syringe structure as used during the reconstitution of the driedpharmaceutical, and in association with a diluent vial;

FIG. 4 is a partial detail view of the outlet end of the syringe, inassociation with an injection needle, as used in the administering ofthe pharmaceutical or medi cine to a patient; and

FIGS. 5 and 6 show alternate methods of reconstitution.

Referring more particularly to the drawings, and first to the explodedview, FIG. 1, there is illustrated an essentially standard syringestructure comprised of a cylinder 10 and a piston 12. The cylinder hasan enlargement or flange 14 at its upper end, the lower end of thecylinder being tapered to provide cylindrical portions 16 and 18 ofsuccessively smaller size. The cylinder member 10 may also be provided,along its length, with an intermediate flange or stop portion 20, thepurpose of which will later be more particularly described.

Referring further to FIG. 1, it will be seen that the piston member 12preferably has a flange portion 22 at its upper end, the piston properof the piston member being formed at the lower end thereof, as indicatedat 24. The piston body may preferably be formed as a plurality ofradially extending wings 26, as is conventional, there being four suchwings illustrated in the present embodiment. As will be understood, thepiston 24-, and wings 26, are adapted to have sliding fit within thecylinder member 10, in the use of the structure.

Preferably the syringe structure, comprising the body member 10 andpiston member 12, may be formed of glass or low cost plastic, providinga single use disposable structure. As will be understood, however, thepiston member or portion 24 is preferably formed of rubber, so that itwill have a proper compressible slidable fit within the cylinder lit),in the use of the structure.

The syringe structure further preferably comprises a cap member 26 and apin member 28 of any suitable material, also shown in FIG. 1, and thepurpose of which will be presently described.

Referring to FIG. 2, it will be seen that the pharmaceutical package ofthe present invention, comprises not syringe structure, but alsopharmaceutical material contained therein, such pharmaceuticalpreferably being in dry lyophilized form, and preferably, in the case ofmultiple component pharmaceuticals, in layered lyophilized form,produced by layered freeze-drying techniques, as more particularly setforth in said Damaskus and Alder patent application to which referencehas hereinbefore been made.

By way of example, the pharmaceutical package, in the particularillustrative embodiment herein set forth,

iay comprise a multiple vitamin composed of a loweriost layer 30 of Bcomplex, an intermediate layer 32 of itamin C or ascorbic acid, and asuperposed or upperiost layer 34 of vitamin B In forming thepharmaceutical package, in accordnce with the present invention, and inaccordance with 1e techniques as set forth in said Damaskus and Alderatent application, the pin 28 is first fitted into the lower- ."iOStcylindrical end 18 of the syringe body into the |osition as shown inFIG. 2, with the knob or handle lOItlOIl 36 of the pin in engagementwith the lowermost .nd of the portion 18. The pin 28 which may be metal)r plastic is adapted to have relatively tight sliding fit vithin theoutlet portion 18 of the syringe body member, as to provide a sealtherewith, when the pin is in as- ;embled position as shown in FIG. 2.Preferably the lower and of the syringe outlet 18 is sterilized, and thepin nandle portion 36 may be immersed within a sealing soluzion, suchfor example as wax, whereby to provide a fluid-tight and hermeticsterile seal.

With the pin 28 in assembled position, as shown in FIG. 2, and with thesyringe body member upright, and the piston member 12 removed, a body ofsterile water may first be poured into the syringe as indicated at 38 inFIG. 2. This water is then frozen to form an ice pellet. Thereafter aliquid solution of B complex is poured into the syringe body, andfrozen, to form the layer 30 of the complex. Thereafter a solution ofascorbic acid is poured onto the frozen layer 30, and itself in turnfrozen to form the frozen layer 32 of vitamin C. Thereafter a solutionof vitamin B is poured onto the frozen pellet or layer 32 of vitamin Cto form the layer 34, which layer is then also frozen to form an icepellet or superposed layer of vitamin material. The entire syringe bodyis then subjected to lyophilization, or freeze-drying techniques, as setforth in said Damaskus and Alder patent application, whereby to providethe vitamin material in freeze-dried form, and specifically in layeredlyophilized form whereby to provide a product having a long shelf lifewith maintained stability and potency, and minimum deterioration andinteraction between the component parts of the product. During thefreeze-drying operation the ice pellet 38 evaporates leaving a spacebelow the lowermost vitamin layer 30, and between such layer and theoutlet end 13 of the syringe body.

After completion of the foregoing, may be applied to the lower end ofshown in FIG. 2, for further protection, and the piston member 12inserted into the syringe body, partially along its length, into theposition shown in FIG. 2. In such position, it will be seen that thepiston member 24 is brought into abutting relationship with theuppermost end of the pin 28, and the piston cannot be further projectedwithout disrupting the position of the pin. Thus when the doctor ornurse receives the package, in the form shown in FIG. 2, if the pin 28has not been disturbed, it is insured that the piston 24 has not beenprojected beyond the position shown in FIG. 2, whereby the sterility ofthe inner wall of the syringe body, below the piston, is insured. Theparts above the piston 24, in the subsequent use of the apparatuspresently to be described, normally do not come into contact with thepharmaceutical product to be administered. Thus pin 28 provides anindicator for the maintained sterility of the product.

Referring to FIG. 3, the parts are shown in the position occupied duringthereconstitution of the pharmaceutical product. More particularly, thecap member 26 and the pin 28 have been removed, and the lower end of thesyringe body has been projected into a container 38, preferablycontaining a quantity of saline solution, or other solution or liquidfor reconstituting the dried pharmaceutical product within the syringebody.

As shown in FIG. 3, as the piston plunger 24 is projected downwardly,and then withdrawn, the reconstitution liquid is drawn from thecontainer 38 into the body the cap member 26 the syringe body, as

10 of the syringe. Abutments or stops 39, formed internally of thecylinder 10, provide an upward stop for the piston, and a stop member 20formed externally of the cylinder optionally may be provided to limitthe penetration of the syringe body into the solution orliquidcontaining vial 38'.

It will further be seen by reference to FIG. 3, that the removal of thepin 23 from the structure leaves a passageway 40 extendinglongitudinally of the syringe through the vitamin layers 30, 32 and 34,whereby to facilitate penetration of the reconstituting liquid into andthrough the layers of the vitamin product, to facilitate thereconstituting of the product, and effect the reconstitution with aminimum of time.

After the reconstituting liquid has been drawn from vial 38' int-o thebody of the syringe, as shown in FIG. 3, the syringe may be shaken orthe like to further facilitate the reconstitution of the pharmaceuticalproduct, as 'will be understood, whereupon a standard injection needle,as indicated at 42 in FIG. 4, may be applied to the lowermost outlet endof the syringe body, for injection of the reconstituted pharmaceuticalproduct into the patient, in accordance with standard administeringtechinques.

Alternate methods of reconstitution are shown in FIGS. 5 and 6. In FIG.5 the vial 38a is provided with a stopper 44 having an opening 46 forreceiving the end 18 of the syringe, said opening being normally closedby a puncturable plastic sheet 48. Upon insertion of the syringe endinto the opening 46 and upon inversion of the vial, the syringe pistonmay be manipulated for reconstitution as before.

In FIG. 6 the needle 42 is applied to the vial prior to reconstitution,and used to puncture the stopper 50 of vial 38b, and withdraws thereconstituted liquid from the vial.

It will thus be seen that in accordance with the present invention apharmaceutical package has been provided, which is composed essentiallyof a standard or conventional syringe, and a contained pharmaceutical,so constructed that by the operation of standard syringe techniques adried pharmaceutical product may be reconstituted, and then administeredto a patient in a rapid and facile manner, and by use of techniques wellknown to operation personnel, without special instruction.

When in layered lyophilized form, the dried pharmaceutical has maximumstability and shelf life, and minimum interaction between the componentparts. The pin 28 not only provides an indicator for the maintainedsterility of the package, until use, but upon removal also provides apassageway through the dried pharmaceutical product, facilitating thereconstitution operation.

In accordance with the present invention, the pharmaceutical product ispackaged directly within an essentially standard syringe, formanipulation of the syringe in accordance with standard techniques, andfor low cost disposability after single use.

It is obvious that various specific embodiment set forth and hereinabovereferred to, without departing from the spirit of the invention. Theinvention is accordingly not to be limited to the specific embodimentshown and described, but only as indicated in the following claims.

The invention is hereby claimed as follows:

1. A pharmaceutical package comprising a syringe, said syringecomprising a cylinder having an outlet and a movable piston within thecylinder, a pharmaceutical comprising a body of material in dry formwithin the cylinder, and a removable pin member within said outlet andprojecting through the pharmaceutical body to provide a perforationtherethrough whereby upon removal of said pin member and uponmanipulation of the piston within the cylinder reconstitution liquid maybe drawn through said outlet and through the perforation in said body tofacilitate the reconstitution thereof.

2. A pharmaceutical package as in claim 1, wherein changes may be madein the means is provided for hermetically sealing the pin member withinthe outlet.

3. A pharmaceutical package as in claim 1, wherein the pin member isprovided with a handle, and wherein a cap member is providedencompassing the handle and mounted upon the outlet end of the syringe.

4. A pharmaceutical package as in claim 1, wherein the pin memberextends longitudinally of the cylindrical syringe body into engagementwith the piston When the piston is in withdrawn position, whereby thepiston cannot be projected within the cylindrical syringe body towardthe outlet end thereof without displacing the pin member.

5. A pharmaceutical package comprising a syringe, said syringecomprising a container and a piston reciprocable therein, said containerhaving a discharge opening, and a pharmaceutical body in dry formdisposed within the container, said body being perforated therethroughwhereby upon the introduction of liquid into the container through saiddischarge opening by manipulation of the piston the liquid will bebrought into contact with the body and through said perforation to bringthe body and liquid into intimate contact for reconstitution.

6. A pharmaceutical package as set forth in claim 5, wherein saidpharmaceutical comprises a lyophilized body having an area substantiallycommensurate with the area of the container chamber and a thicknesssubstantially less than the length of the container chamber tofacilitate the reconstitution of said body Within the container.

7. A pharmaceutical package as set forth in claim 5, wherein saidpharmaceutical body is in the form of a perforated stratum within thesyringe.

8. A pharmaceutical package as set forth in claim 5, wherein thepharmaceutical body is in the form of superposed strata of lyophilizedmaterial within the syringe.

9. A pharmaceutical package as set forth in claim 5, wherein stop meansis provided on the container for limiting the movement of the pistonwithin the container in a direction away from said discharge opening.

References Cited UNITED STATES PATENTS 1,247,678 11/1917 Hentschel.1,466,132 8/ 1923 Lippert. 2,195,429 4/ 1940 Shaler. 2,862,616 12/1958Capozzi et al. 2,982,396 5/1961 Shihadeh. 3,107,785 10/1963 Roche 20643X THERON E. CONDON, Primary Examiner. I. M. CASKIE, Assistant Examiner.

1. A PHARMACEUTICAL PACKAGE COMPRISING A SYRINGE, SAID SYRINGECOMPRISING A CYLINDER HAVING AN OUTLET AND A MOVABLE PISTON WITHIN THECYLINDER, A PHARMACEUTICAL COMPRISING A BODY OF MATERIAL IN DRY FORMWITHIN THE CYLINDER, AND A REMOVABLE PIN MEMBER WITHIN SAID OUTER ANDPROJECTNG THROUGH THE PHARMACEUTICAL BODY TO PROVIDE A PERFORATIONTHERETHROUGH WHEREBY UPON REMOVAL OF SAID PIN MEMBER AND UPONMANIPULATION OF THE PISTON WITHIN THE CYLINDER RECONSTITUTION LIQUID MAYBE DRAWN THROUGH